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Lung Infection Caused By A Little-known Bacterium May Be Less Transmissible Than Thought
A little-known bacterium—a distant cousin of the microbes that cause tuberculosis and leprosy—is emerging as a public health threat capable of causing severe lung infections among vulnerable populations, those with compromised immunity or reduced lung function.
Previous research had found that various strains of the bacterium Mycobacterium abscessus were genetically similar, stoking fears that it was spreading from person to person.
But a new study by Harvard Medical School researchers, published May 22 in PNAS, calls those findings into question, offering an alternative explanation behind the genetic similarity of clinical clusters. This suggests that the pathogen may not be that prone to person-to-person transmission after all.
"Our findings make a strong case for a different explanation behind the observed genetic similarities across strains," said study senior author Maha Farhat, the Gilbert S. Omenn Associate Professor of Biomedical Informatics at HMS and a pulmonary disease expert at Massachusetts General Hospital. Farhat conducted the work in collaboration with Eric Rubin's lab at the Harvard T.H. Chan School of Public Health.
The results, Farhat added, argue against direct person-to-person transmission in clinical settings and instead point to M. Abscessus infections being acquired from the home or other environmental exposures.
In addition to having implications for the precautions that hospitals take to prevent outbreaks, it's an important new clue into the behavior of a relatively unknown pathogen that poses serious risks for vulnerable populations.
The research not only contributes to the understanding of M. Abscessus transmission, but also suggests scientists should be cautious about assuming human transmission when they see genetic similarities in pathogens more generally, said study first author Nicoletta Commins, who conducted the research as a doctoral candidate at HMS and is now a postdoctoral fellow at the Broad Institute.
"Our results certainly do not refute the possibility of person-to-person transmission of Mycobacterium abscessus in some cases, and more research is needed to inform best clinical practice for vulnerable patients," she said. "However, our work supports a model in which person-to-person transmission may not be as common as it is sometimes suggested to be."
M. Abscessus is a hardy microbe highly resistant to antibiotics and can infect the lungs of immunocompromised people. While it doesn't pose a threat to most healthy individuals, it can cause severe infection in those with suppressed immunity or people with compromised lung function such as patients with cystic fibrosis, a genetic condition marked by recurrent lung infections and lung scarring. Notably, patients with CF who become infected with this organism become ineligible for lifesaving lung transplants.
The earlier study that sounded the alarm about person-to-person transmission was based on genetic sequencing of M. Abscessus samples obtained from cystic fibrosis patients at clinics in the United States, Australia, and Europe, including the United Kingdom. Researchers found few genetic mutations across the samples—a possible sign that the pathogen was spreading directly between humans.
For many pathogens such as TB, for example, recent person-to-person transmission leads to only a few or no mutations between any pair of samples simply because the pathogen does not have much time to acquire genetic mutations, Farhat explained.
"Understandably, observing the genetic similarity between M. Abscessus samples caused a great deal of anxiety and fear around how these organisms could be transmitting," she said.
Clinicians, especially in clinics that treat cystic fibrosis patients, began taking extra precautions to avert transmission. However, follow-up investigations failed to find supporting evidence that human-to-human transmission was happening, raising questions about other possible explanations for the genetic similarities across samples.
Farhat's team set out to investigate a hypothesis that the samples appeared genetically similar because the pathogen was evolving at a very slow rate.
"We thought, yeah, you observed a small number of mutations, but we don't know how quickly these mutations are acquired, she explained. "It may be slower than we think, and links between samples that appear recent may not be.'"
The scientists first used a large dataset of M. Abscessus genomes to create a "tree of life," a kind of genetic family tree for the bacterium.
They looked at branches of the tree with clusters of genetically similar strains, then tried to calculate their evolutionary rate. They found that these genetically similar clusters were evolving around 10 times more slowly than typical M. Abscessus strains.
Next, they used computer modeling to determine whether the genetic similarities could be explained by the relatively small population size of these bacteria. But even when they simulated extreme population sizes, the result didn't change. This was an indicator that the high genetic similarity is best explained by a slower evolutionary rate.
Finally, researchers conducted experiments to see how fast different strains of M. Abscessus evolved to develop resistance when exposed to antibiotics in the lab. They found that the genetically similar strains evolved much more slowly than other strains.
"These are three separate lines of evidence supporting this idea that these clustered isolates of Mycobacterium abscessus are evolving at a slower rate," Farhat said.
In addition to reducing concern about person-to-person transmission, the findings provide new insight into a poorly understood pathogen.
In particular, the results offer clues about how a bug found primarily in the environment adapts and changes after it enters the human body—information that could help scientists eventually understand how to prevent and treat infections.
Farhat is now planning follow-up studies that would compare bacteria in the environment with samples taken from patients, to better understand why certain patients become infected.
Additional study authors include Mark R. Sullivan, Kerry McGowen, Evan Koch, and Eric Rubin.
More information: Nicoletta Commins et al, Mutation rates and adaptive variation among the clinically dominant clusters of Mycobacterium abscessus, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2302033120
Citation: Lung infection caused by a little-known bacterium may be less transmissible than thought (2023, May 30) retrieved 26 June 2023 from https://medicalxpress.Com/news/2023-05-lung-infection-little-known-bacterium-transmissible.Html
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Treatment For Nontuberculous Mycobacterial Lung Disease
If you're diagnosed with nontuberculous mycobacterial lung disease, your doctor will discuss the right treatment for you.
Some people with NTM lung disease don't need treatment. Others require ongoing treatments to keep their disease under control.
Your doctor may decide to watch and wait rather than treat your infection. They can check your symptoms and look at X-rays to make sure your lungs don't start to show damage.
Why wouldn't you want to treat your infection even if it's mild? You'll need to take antibiotics. They have side effects. And you'll probably need more than one type because the bacteria often become resistant to drugs. Your doctor will weigh the pros and cons of treating your disease right away.
If your doctor does choose to treat it, you'll take the medicine for a while. The doctor will run a sputum culture test every month or two to look for bacteria. You'll cough up some mucus and they'll send it to a lab for tests. You can stop taking the meds when the results have come back negative for a year.
Your doctor will decide which antibiotic to try first based on:
Most people with an NTM lung infection start with a combination of antibiotics that they take three times a week. You may have to change medications if the bacteria become resistant to your doctor's first choice, but they have several options to choose from.
Doctors treat mycobacterium avium complex (MAC) disease, the most common NTM lung infection, with a combination of three antibiotics:
If you have more severe MAC disease that results from cavities in your lungs, your doctor may try rifabutin (Mycobutin) instead of rifampin (Rifadin, Rimactane). They might add amikacin or streptomycin three times a week early in your treatment.
If you have HIV, too, you're at higher risk for disseminated MAC disease. It causes symptoms all over your body like night sweats, weight loss, fever, and anemia. Treatment involves taking two medications. Studies show that using just one medicine is not effective and causes bacterial resistance. You'll be given azithromycin or clarithromycin along with ethambutol. This is called double therapy. If needed, you might also take rifabutin, which is considered triple therapy.
If you have AIDS and CD4+ T-lymphocyte counts less than 50 cells/microliter, you can try to prevent disseminated MAC disease with azithromycin or clarithromycin. Rifabutin is another option, but it may be harder on your system.
If you're infection is from M. Kansasii bacteria, you'll probably take a mix of azithromycin, ethambutol, and rifampin once a day for 1 year or until your sputum test is negative.
If you have an M. Abscessus lung infection, antibiotics alone may not work. Clarithromycin along with other drugs may help control your symptoms and keep the disease from getting worse. You might need surgery to remove damaged parts of your lung, too.
All antibiotics for NTM lung disease have side effects. They can be hard on your liver or kidneys, cause hearing loss or tinnitus (ringing in your ears), or severe upset stomach.
Your doctor may need to switch your medicines or lower your dose if one medicine causes a serious reaction. If you notice sudden problems with your hearing or eyesight, or pain or numbness in your hands or feet, call them right away.
Antibiotics alone may not clear up your infection or ease your symptoms. Some people also need surgery to take out damaged lung tissue.
Surgery along with antibiotics can clear up an NTM lung infection in many people.
But if you cough up blood after you've taken antibiotics, surgery may be a next step.
There are other things you can try to ease your symptoms and help clear up your infection. You don't do them instead of your medicines, but as an add-on. Talk to your doctor first if you'd like to try any of these therapies:
You can also:
Once you treat your NTM lung disease, you can take steps to prevent another infection. These bacteria are often found in water or moist places, so take these easy steps:
Lung disease symptoms and the treatments for them may make you feel awful at times. At any point in your life with lung disease, ask your doctor about palliative care to help you feel more comfortable.
Palliative care is any treatment that helps to ease symptoms or just make you feel better. You may need oxygen therapy to help you breathe more easily, take meds for your upset stomach, or see a counselor to deal with stress.
Counseling or support groups of other people with lung disease can help you manage depression or anxiety. Check out groups in your area or online. Let your doctor know if your lung disease makes you feel depressed or hopeless, so you can get treatment right away.
Lung Infection May Be Less Transmissible Than Thought
A little-known bacterium — a distant cousin of the microbes that cause tuberculosis and leprosy — is emerging as a public health threat capable of causing severe lung infections among vulnerable populations, those with compromised immunity or reduced lung function.
Recent research found that various strains of the bacterium, Mycobacterium abscessus, were genetically similar, stoking fears that it was spreading from person to person.
But a new study by Harvard Medical School researchers published May 22 in PNAS, calls those findings into question, offering an alternative explanation behind the genetic similarity of clinical clusters. This suggests that the pathogen may not be that prone to person-to-person transmission after all.
"Our findings make a strong case for a different explanation behind the observed genetic similarities across strains," said study senior author Maha Farhat, the Gilbert S. Omenn Associate Professor of Biomedical Informatics at HMS and a pulmonary disease expert at Massachusetts General Hospital. Farhat conducted the work in collaboration with Eric Rubin's lab at the Harvard T.H. Chan School of Public Health.
The results, Farhat added, argue against direct person-to-person transmission in clinical settings and instead point to M. Abscessus infections being acquired from the home or other environmental exposures.
In addition to having implications for the precautions that hospitals take to prevent outbreaks, it's an important new clue into the behavior of a relatively unknown pathogen that poses serious risks for vulnerable populations.
The research not only contributes to the understanding of M. Abscessus transmission, but also suggests scientists should be cautious about assuming human transmission when they see genetic similarities in pathogens more generally, said study first author Nicoletta Commins, who conducted the research as a doctoral candidate at HMS and is now a postdoctoral fellow at the Broad Institute.
"Our results certainly do not refute the possibility of person-to-person transmission of Mycobacterium abscessus in some cases, and more research is needed to inform best clinical practice for vulnerable patients," she said. "However, our work supports a model in which person-to-person transmission may not be as common as it is sometimes suggested to be."
M. Abscessus is a hardy microbe highly resistant to antibiotics and can infect the lungs of immunocompromised people. While it doesn't pose a threat to most healthy individuals, it can cause severe infection in those with suppressed immunity or people with compromised lung function such as patients with cystic fibrosis, a genetic condition marked by recurrent lung infections and lung scarring. Notably, patients with CF who become infected with this organism become ineligible for lifesaving lung transplants.
The earlier study that sounded the alarm about person-to-person transmission was based on genetic sequencing of M. Abscessus samples obtained from cystic fibrosis patients at clinics in the United States, Australia, and Europe, including the United Kingdom. Researchers found few genetic mutations across the samples — a possible sign that the pathogen was spreading directly between humans.
For many pathogens such as TB, for example, recent person-to-person transmission leads to only a few or no mutations between any pair of samples simply because the pathogen does not have much time to acquire genetic mutations, Farhat explained.
"Understandably, observing the genetic similarity between M. Abscessus samples caused a great deal of anxiety and fear around how these organisms could be transmitting," she said.
Clinicians, especially in clinics that treat cystic fibrosis patients, began taking extra precautions to avert transmission. However, follow-up investigations failed to find supporting evidence that human-to-human transmission was happening, raising questions about other possible explanations for the genetic similarities across samples.
Farhat's team set out to investigate a hypothesis that the samples appeared genetically similar because the pathogen was evolving at a very slow rate.
"We thought, yeah, you observed a small number of mutations, but we don't know how quickly these mutations are acquired, she explained. "It may be slower than we think, and links between samples that appear recent may not be.'"
The scientists first used a large dataset of M. Abscessus genomes to create a "tree of life," a kind of genetic family tree for the bacterium.
They looked at branches of the tree with clusters of genetically similar strains, then tried to calculate their evolutionary rate. They found that these genetically similar clusters were evolving around 10 times more slowly than typical M. Abscessus strains.
Next, they used computer modeling to determine whether the genetic similarities could be explained by the relatively small population size of these bacteria. But even when they simulated extreme population sizes, the result didn't change. This was an indicator that the high genetic similarity is best explained by a slower evolutionary rate.
Finally, researchers conducted experiments to see how fast different strains of M. Abscessus evolved to develop resistance when exposed to antibiotics in the lab. They found that the genetically similar strains evolved much more slowly than other strains.
"These are three separate lines of evidence supporting this idea that these clustered isolates of Mycobacterium abscessus are evolving at a slower rate," Farhat said.
In addition to reducing concern about person-to-person transmission, the findings provide new insight into a poorly understood pathogen.
In particular, the results offer clues about how a bug found primarily in the environment adapts and changes after it enters the human body — information that could help scientists eventually understand how to prevent and treat infections.
Farhat is now planning follow-up studies that would compare bacteria in the environment with samples taken from patients, to better understand why certain patients become infected.
Authorship, funding, disclosures
Additional authors included Mark R. Sullivan, Kerry McGowen
Evan Koch, and Eric Rubin. The work was partly supported by the Damon Runyon Cancer Research Foundation, DRG-2415-20, with additional support from the Orchestra High Performance Compute Cluster at Harvard Medical School, funded by the NIH NCRR 1S10RR028832-01.
JournalProceedings of the National Academy of Sciences
Article TitleMutation rates and adaptive variation among the clinically dominant clusters of Mycobacterium abscessus
Article Publication Date22-May-2023
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